ABSTRACT Anxiety disorders are the most common mental illness in the United States and affect more women than men. Chronic avoidance of external threats and negative thoughts/feelings is a prominent diagnostic feature. Yet, we lack psychiatric or biological assays to measure or predict functional outcomes and guide treatments for reducing avoidance. We thus need etiological models grounded in theory and human research to clarify neural markers of vulnerability to avoidance in men and women and aid development of tailored, sex-specific interventions. This application draws on affective and decision neuroscience to address how activation associated with avoidant decision-making differs between anxious individuals and those with low anxiety. We couple a behavioral model of real-world social approach-avoidance (AP-AV) decision-making with fMRI to measure signaling of social reward-threat value differences and outcomes. Our model suggests the dorsal anterior cingulate (dACC) and dorsal medial prefrontal cortex (dmPFC) signal value differences between approach and avoidance actions, while the ventromedial prefrontal cortex (vmPFC) signals value of reward and threat outcomes. Anterior insula (AI) signals of threat and ventral striatum (VS) signals of reward also interplay. Preliminary data show that individuals with high experiential avoidance base choices to approach/avoid on distinctively altered signaling of reward-threat value differences and outcomes. Such biased signaling could explain excessive avoidance or suggest potential mechanisms. We propose two neuroimaging experiments designed to determine whether altered signaling reflects a stable neuropathology in anxiety disorders or whether threat/reward manipulations common to behavioral treatments can normalize signaling and increase approach behavior. For each we will recruit healthy (25M/25F) and clinically anxious (25M/25F) 18-35 yr-old adults matched on age, sex, ethnicity, SES, and IQ (total N=200). We aim to determine the extent to which anxiety modulates signaling and (1) decreased threat increases approach behavior and normalizes signaling and connectivity; (2) increased reward increases approach behavior and normalizes signaling and connectivity; and (3) sex modulates signaling of reward-threat value differences and outcomes. Completion of our aims will yield a detailed understanding of neural mechanisms of avoidant decision-making in anxiety, responsiveness to reward-threat value differences, and sex differences.